L-Arginine-induced acute pancreatitis and its associated lung injury in rats: Down-regulation of TLR-۴/MAPK-p۳۸/JNK signaling pathway via Ginkgo biloba extract EGb ۷۶۱

Objective(s): Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study aimed to examine the efficacy of Ginkgo biloba extract EGb ۷۶۱ (GBE) in the treatment of L-arginine-induced AP and its associated lung injury. Materials and Methods: Forty rats were randomly assigned into four groups. The normal group received only saline intraperitoneally while the other groups received two intraperitoneal L-arginine injections (۲۵۰ mg/۱۰۰ g b.wt) separated by a ۱-hour interval to provoke AP. GBE (۲۰۰ and ۴۰۰ mg/kg/day, PO) was administered for ۲ weeks post-induction of pancreatitis. Sera and pancreatic tissues were isolated.Results: The outcome of the present study revealed that GBE ameliorated the elevated levels of serum amylase, lipase, and pancreatic inflammatory mediators viz., tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase P۳۸ (MAPK-P۳۸), c-Jun N-terminal kinase ۱ (JNK۱), and nuclear factor-kappa B (NF-κB). Moreover, GBE restored the pancreatic gene expression of Toll-like receptor ۴ (TLR۴) and prostatic acid phosphatase-۲ (PAP-۲). Pancreatic and lung histopathological examinations confirmed the aforementioned parameters. Conclusion: GBE interfered with the mechanistic pathway of L-arginine-induced acute pancreatic and its associated lung injury. Due to its anti-inflammatory properties, GBE can be used as a novel therapeutic candidate for the treatment of AP through down-regulating TLR-۴/MAPK-p۳۸/JNK and MAPK- p۳۸/NF-κB signaling cascades.

کلیدواژه ها:

Acute pancreatitis ، Ginkgo biloba ، Inflammation ، L-arginine ، Lung injury ، Rats